MicroRNAs or miRNAs are small noncoding RNAs which function by regulating target gene expression post-transcriptionally. The breadth of genetic regulatory effects potentially mediated by microRNAs and their central role in diverse cellular and developmental processes (Ambrose (2004) Nature 431 (7006):350-5; Bartel & Chen (2004) Nat. Rev. Genet. 5 (5):396-400; Miska (2005) Curr. Opin. Genet. Dev. 15 (5):563-8; Sevignani, et al. (2006) Mamm. Genome 17 (3):189-202) has lead to the suggestion that aberrant expression of microRNA genes could contribute to human disease, including cancer (McManus (2003) Semin. Cancer Biol. 13 (4):253-8; Caldas & Brenton (2005) Nat. Med. 11 (7):712-4; Lu, et al. (2005) Nature 435 (7043):834-8; Croce & Calin (2005) Cell 122 (1):6-7). A substantial number of microRNA genes are located in genomic regions that are frequently amplified, deleted, or rearranged in cancer, providing further evidence of a role for microRNAs in cancer pathogenesis (Calin, et al. (2002) Proc. Natl. Acad. Sci. USA 99 (24):15524-9; Nairz, et al. (2006) Dev. Biol. 291 (2):314-24). Deregulated microRNA expression has been documented in diverse cancers including lymphoma (Tagawa & Seto (2005) Leukemia 19 (11):2013-6; He, et al. (2005) Nature 435 (7043):828-33; Costinean, et al. (2006) Proc. Natl. Acad. Sci. USA 103 (18):7024-9; Kluiver, et al. (2006) Genes Chromosomes Cancer 45 (2):147-53 11-14), colorectal cancer (Michael, et al. (2003) Mol. Cancer Res. 1 (12):882-91), lung cancer (Hayashita, et al. (2005) Cancer Res. 65 (21):9628-32), breast cancer (Iorio, et al. (2005) Cancer Res. 65 (16):7065-70), and glioblastoma (Ciafre, et al. (2005) Biochem. Biophys. Res. Commun. 334 (4):1351-8; Chan, et al. (2005) Cancer Res. 65 (14):6029-33). Specific microRNAs have been shown to target genes critical for the development of cancer such as E2F (O'Donnell, et al. (2005) Nature 435 (7043):839-43) and RAS (Johnson, et al. (2005) Cell 120 (5):635-47). Hence, microRNAs and the genes they regulate can potentially provide etiologic insights as well as serve as both diagnostic markers and therapeutic targets for many different tumor types.
Gliomas are tumors that occur in the central nervous system and demonstrate invasive growth. Glioblastomas in particular are the most resistant to treatment, and have an extremely poor five-year survival rate of about 8%. Although definitive efficacy of chemotherapy has only been confirmed for alkylating agents and temozolomide, their efficacy is limited to concomitant use with radiotherapy. On the other hand, post-surgical radiotherapy has been recognized to demonstrate life-prolonging effects. Knowledge of molecular biomarkers that are associated with genetic regulatory mechanisms contributing to malignancy is essential for elucidating the mechanisms underlying malignant transformation, for understanding pathologic attributes of Glioblastoma Multiforme (GBM), and ultimately for designing effective strategies for GBM treatment. MicroRNAs encoded by the microRNA-10 gene have been identified as molecular biomarkers of GBM (Gaur, et al. (2007) Cancer Res. 67:2456-68; Sasayama, et al. (2009) Int. J. Cancer 125 (6):1407-13; Ciafre, et al. (2005) supra). In addition, mRNA expressions of RhoC and urokinase-type plasminogen activator receptor (uPAR), which were thought to be regulated by miR-10b via HOXD10 (homeobox D10), have been correlated with the expression of miR-10b, as were the protein expression levels of RhoC and uPAR (Sasayama, et al. (2009) supra).